Epigenetic Specificities of the Human Microbiota Along the Digestive Tract From the Oral Cavity to the Colon - Presentation

The holobiont concept defines the human organism as an integrated biological system composed of the host and its associated microbiota, forming a functional hologenome. Increasing evidence indicates that host-microbiota interactions extend beyond metabolic and immunological functions to include epigenetic regulation of gene expression. The aim of this narrative review is to synthesise and critically examine current literature regarding microbiota-driven epigenetic mechanisms along the digestive tract. A targeted literature search was performed using relevant databases, and selected studies were evaluated according to their contribution to understanding microbiota–epigenome interactions. Particular attention is given to DNA methylation, histone modifications, and microRNAs (miRNA)-mediated regulation, as well as to representative microbial species such as Porphyromonas gingivalis, Helicobacter pylori, and Faecalibacterium prausnitzii. Segment-specific effects are discussed in relation to immune modulation, epithelial integrity, carcinogenesis, and metabolic adaptation. The potential influence of maternal microbiota, microbiota-gut-brain interactions, and the persistence or reversibility of epigenetic modifications are also considered. Perinatal influences, the persistence and reversibility of epigenetic modifications, and the conceptual limitations of hologenomic interpretations are also addressed. However, many currently proposed mechanisms are supported mainly by experimental models, in vitro studies, or observational human data, and their causal relevance requires further validation. This narrative review aims to provide a balanced and integrative perspective on microbiota–epigenome interactions, emphasizing both their biological relevance and the current limitations and need for further validation in human studies.